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Review
. 2010 Jun;99(6):2557-75.
doi: 10.1002/jps.22054.

Delivery of therapeutic proteins

Dipak S Pisal  1 , Matthew P Kosloski, Sathy V Balu-Iyer
Affiliations
Review

Delivery of therapeutic proteins

Dipak S Pisal et al. J Pharm Sci. 2010 Jun.

Abstract

The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g., liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches.

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Figures

Figure 1
Figure 1. Structural formulae of polyethylene glycol molecules
The basic structural formulae for linear PEG, mPEG, and branched mPEG are shown.
Figure 2
Figure 2. Products of common PEG activation chemistries
(a) Cyanuric chloride method. (b) Imidazole formate method. (c) Succinimidyl carbonates of PEG. (d) PEG-succinimidyl succinate method. [adapted from52]
Figure 3
Figure 3. Liposome structures and modifications
3A. Common structural arrangements for lipid based drug delivery vehicles. 3B. Schematic of the structure of a typical liposome with several of the potential covalent modifications depicted.
Figure 4
Figure 4. Size comparison of nano and micro particulate delivery systems
A sample microsphere, multilamellar liposome, large unilamellar liposome, and small unilamellar liposomes are presented to scale for size comparison. Microspheres may be up to 25× the diameter shown here.
See this image and copyright information in PMC

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